1. Field Of The Invention
The present invention relates generally to instruments for measuring the concentration of elements, compounds and gases in a fluid or gaseous mixture, and more particularly, to a method for homogeneously dispersing an analyte-sensitive indicator substance throughout an analyte-permeable matrix using emulsion-related techniques. The method produces an improved sensor element that is particularly suitable for use with a number of methods and instruments for measuring the content of an analyte in a sample.
2. Description Of The Prior Art
The development of instruments and methods for measuring the concentration of elements and compounds in liquids and gaseous mixtures has been a tremendous breakthrough in many science-related fields, particularly the medical arts. Medical instruments are available for performing in vivo measurements of blood chemistry to determine, for example, pH and the partial pressures of gases, such as carbon dioxide and oxygen, in a patient's blood stream. These instruments use specially adapted catheters, optical fibers and sensor elements that can be placed directly in a blood vessel, muscle, or other bodily tissue of a patient. These implanted devices are generally safe, economical, and can be manufactured from material that permits long term implantation in the body. As a result, physicians can continually monitor the blood chemistry of a patient, eliminating the need to constantly draw blood for laboratory analysis.
Many different forms of analyte-measuring instruments have been designed and developed throughout the years for use in numerous medical and industrial applications. Among the many used methods and instruments are those that rely on optical properties of the sensing element. This process may use a dye made from certain organic substance that is sensitive to a particular analyte. When the dye interacts with the analyte in a liquid or gaseous sample, the dye undergoes a physical change that is directly measurable. This change is usually a physical property of the dye, such as its luminescence or fluorescence intensity or decay time. The change of this physical property is directly related to the concentration of the analyte in the sample.
The analyte-sensitive substance, also called an indicator, is arranged in a sensor element which can be stored in a permeable membrane which allows the analyte to permeate and interact with the indicator while preventing other analytes and fluids from reaching the indicator. The sensor element is usually first placed in the test sample to allow the analyte to interact with the indicator and is then subjected to an external source of excitation, usually a light source, that measures the change in the intensity of the physical characteristic of the indicator. Since the concentration of the analyte is directly related to the difference of intensity, a change in the intensity can be used to calculate the proportion of the analyte present in the sample.
Early devices utilized a monochromatic light beam to determine the intensity of fluorescence of the indicator. These devices used optical lenses and prisms for focusing the monochromatic light onto an external sensing element, or optode, which included a permeable membrane, much like an envelope or bladder, which stored the indicator substance. This membrane acted as a barrier which separated the indicator substance from the fluid being analyzed. While somewhat successful, these early optodes presented a number of problems which hindered performance. For example, these membranes were particularly vulnerable if a slight crack developed either during storage or in use since the indicator would leak out. Also, the indicator had a tendency to leach out of the membrane, especially if the membrane came in contact with a substance having similar properties. As a result of this leakage, the character of the indicator would change and affect the accuracy of any measurement.
The development of glass or optical fibers provided a new source for directing the light source to the sensor element. Optical fiber sensing instruments utilize a relatively similar principle for determining the content of an analyte in a sample. Light generated from an external instrument travels along the optical fiber to the sensor element incorporating the indicator substance which is placed at the distal end of the fiber. The light is then transmitted back from the sensing element to an external detection instrument that measures the change of intensity of the indicator.
Other optical systems utilize multiple optical fibers and a sensor element that is remotely located on a catheter or similar device. These systems include at least one light transmitting optical fiber which is placed in close alignment with the remote sensor element and a second output fiber that carries the irradiated light from the sensor to the external detection instrument.
The use of optical fibers required the development of new sensor elements that could be contained in a compact geometry. These elements had to be, of course, much smaller than the conventional bladder-type optode. Also, due to the thin diameter of the fiber, the use of bladders or envelops were generally not feasible due to their relatively large size. Some bladder retaining sensors were developed, but suffered from the same leaking and leaching problems that confronted the earlier optodes.
Alternative solutions for creating a usable sensor included dispersing particles containing an indicator in an analyte-permeable matrix. These sensor proved to be much smaller than conventional optodes, but they too had similar problems of leaching and were vulnerability to cracks that allow the indicator to leak from the matrix. Also, the size of these sensors were directly subject to the thickness of the largest indicator containing particle. Other disadvantages included uneven distribution of the indicator throughout the matrix which caused variations between sensors made from similar materials.
Accordingly, those concerned with the development and use of optical fiber sensing devices have recognized the need for improving the sensor element which contains the indicator substance. Preferably, an improved sensor element should be capable of easy application to an optical fiber and should be capable of being manufactured in a thin profile. The sensor element should have an even dispersal of the indicator throughout the permeable membrane and should not be vulnerable to small cracks that could render the sensor useless. Furthermore, it would be extremely advantageous if such a sensor element could be used with a variety of analyte measuring systems and capable of being applied to the optical fiber in one manufacturing step.